tsRNA-15797-modified BMSC-derived exosomes mediate LFNG to induce angiogenesis in osteonecrosis of the femoral head.

Abstract

Background: Osteonecrosis of the femoral head (ONFH) is an ischemic disease characterized by the impairment of angiogenesis. We have previously elucidated the role of tsRNAs and BMSC exosomes in ONFH, but whether tsRNA-modified BMSC exosomes promote angiogenesis in ONFH remains unclear.

Methods: The expression of angiogenesis-related tsRNA in plasma exosomes from ONFH patients was examined by q-PCR. The function of tsRNA in HUVECs was identified by CCK-8 and angiogenesis assay. Exosomes purified from tsRNA-15797 overexpressed BMSCs were cocultured with HUVECs to examine their role in angiogenesis. The molecule mechanism of tsRNA-15797-modified exosomes was explored by RNA sequencing, dual-luciferase assay, and immunofluorescence.

Results: A tRNA-derived small RNA tsRNA-15797 was down-regulated in plasma exosomes of ONFH patients. We found the effects of BMSCs-derived exosomes on accelerating HUVECs angiogenesis and migration, which were further enhanced after overexpressing tsRNA-15797. Besides, overexpression of tsRNA-15797 would lead to down-regulation of LFNG correlated with angiogenesis. tsRNA-15797 could directly interact with LFNG. We demonstrated that LNFG overexpression weakened the pro angiogenic and migratory effects of tsRNA-15797-modified BMSCs-derived exosomes.

Conclusion: We successfully constructed tsRNA-15797-modified BMSC-derived exosomes and demonstrated that it induced the angiogenesis of HUVECs by targeting the down-regulation of LFNG. Thus, tsRNA-15797-loaded BMSCs-derived exosomes may be a potential target therapy drug for ONFH.